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Oral Budesonide in the Treatment of Patients With Primary Biliary Cirrhosis and Overlap Features of Autoimmune Hepatitis (PBC)

Primary Purpose

Primary Biliary Cirrhosis, Autoimmune Hepatitis

Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Budesonide
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Biliary Cirrhosis focused on measuring Urso, Budesonide, PBC, overlap AIH, PBC with overlap features of autoimmune hepatitis

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Chronic cholestatic liver disease for greater than 6 months with alkaline phosphatase levels greater than 2 times the upper limit of normal.
  • Positive AMA titer 1:40 or AMA > 1.0 U.
  • Liver histology in the past (available for review) with features consistent with or diagnostic of PBC
  • Ultrasound, computed tomography (CT), or cholangiography of the biliary tree which excludes biliary obstruction.
  • The diagnosis of AIH necessary for evaluation of PBC-AIH overlap syndrome will be based on the revised International Autoimmune Hepatitis Group (IAHG) Scoring System.

Exclusion Criteria:

  • Patients with other serious coexistent conditions such as pre-existing advanced malignancy or severe cardiopulmonary disease which would be expected to limit their expectancy to less than three years.
  • Patients unable to provide informed consent.
  • Treatment with methotrexate, corticosteroids, azathioprine, chlorambucil, cyclosporin, penicillamine, colchicine or chenodeoxycholic acid in the preceding three months.
  • Anticipated need for transplantation in one year (Mayo survival model <80% one-year survival without transplant).
  • Liver biopsy revealing stage IV disease.
  • Evidence of portal hypertension such as esophageal varices, portal gastropathy, ascites or hepatic encephalopathy.
  • Known history of portal vein thrombosis.
  • Evidence of osteoporosis.
  • Serum bilirubin >4 mg/dl.
  • Age less than 21 years of age or greater than 75 years of age.
  • Pregnancy.
  • Breast-feeding.
  • Active drug or alcohol use.
  • Findings highly suggestive of liver disease of other etiology such as chronic alcoholic liver disease, chronic hepatitis B or C infection, hemochromatosis, Wilson's disease, 1-antitrypsin deficiency, non-alcoholic steatohepatitis or sclerosing cholangitis.
  • Serum creatinine over 2.0 mg/dl.
  • History of documented active peptic ulcer disease in preceding year.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    1

    Arm Description

    Single arm, active treatment

    Outcomes

    Primary Outcome Measures

    The main endpoint will be the percentage of patients with improvement in alkaline phosphatase to less than 1.5 times normal over one year and the percentage of patients with a reduction in their Mayo Risk Score over one year.

    Secondary Outcome Measures

    Effects of UDCA & budesonide on serum levels of alk phos, AST, total bilirubin, albumin, and prothrombin time, Mayo risk score and toxicity and tolerability of the budesonide/UDCA regimen, including effects on bone density.

    Full Information

    First Posted
    December 21, 2007
    Last Updated
    October 1, 2010
    Sponsor
    Mayo Clinic
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00587119
    Brief Title
    Oral Budesonide in the Treatment of Patients With Primary Biliary Cirrhosis and Overlap Features of Autoimmune Hepatitis
    Acronym
    PBC
    Official Title
    Open-Label Pilot Study Evaluating Oral Budesonide in the Treatment of Patients With Primary Biliary Cirrhosis and Overlap Features of Autoimmune Hepatitis.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2010
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Lack of enrollment
    Study Start Date
    December 2007 (undefined)
    Primary Completion Date
    July 2009 (Actual)
    Study Completion Date
    July 2009 (Anticipated)

    3. Sponsor/Collaborators

    Name of the Sponsor
    Mayo Clinic

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of the study is to find out the effects Budesonide, 9 mg daily for one year, has on patients with Primary Biliary Cirrhosis with features of autoimmune hepatitis.
    Detailed Description
    Pilot Study of Budesonide for Primary Biliary Cirrhosis with overlap features of Autoimmune Hepatitis Primary biliary cirrhosis (PBC) is a chronic liver disease of unknown cause that may result in inflammation and destruction of the bile ducts inside the liver. Over time, cirrhosis and complications of liver failure may develop. Although treatment with ursodiol has been association with a reduction in liver enzymes (blood tests) and a reduction in the progression of the disease, some patients do not respond to ursodiol therapy. Patients with overlap features of Autoimmune Hepatitis (AIH) appear to be at higher risk of developing complications of disease even when on ursodiol. The purpose of this study is to evaluate the effects and safety of Budesonide in PBC with overlap features of AIH. Budesonide has unique effects on the immune system that may be helpful in the treatment of the disease. Eligible participants will include those patients with a diagnosis of PBC with overlap features of AIH and in whom liver enzymes have not sufficiently improved with ursodiol therapy (the alkaline phosphatase is not less than twice upper normal). At entry all patients will have a history and physical examination, blood tests, bone densitometry and complete quality of life questionnaires. Patients will be prescribed Budesonide 9 mg to take daily for one year in addition to the ursodiol. The medication can be taken with or without food. Blood tests and symptoms diaries will be completed every 3 months. Patients will be contacted by phone to assess tolerance of the medication and any new health problems. At one year, patients will return for a history and physical and repeat blood tests and bone densitometry. Possible side-effects include bone mass loss (bone thinning), diarrhea, indigestion, nausea, joint pains, dizziness, headaches, weight gain and Cushing's syndrome. Other side-effects are possible. The medication and the tests will be billed to the patient or patient's insurance.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Primary Biliary Cirrhosis, Autoimmune Hepatitis
    Keywords
    Urso, Budesonide, PBC, overlap AIH, PBC with overlap features of autoimmune hepatitis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    1
    Arm Type
    Experimental
    Arm Description
    Single arm, active treatment
    Intervention Type
    Drug
    Intervention Name(s)
    Budesonide
    Other Intervention Name(s)
    Entocort
    Intervention Description
    Oral Budesonide, 3 mg three times daily, will be given for 1 year.
    Primary Outcome Measure Information:
    Title
    The main endpoint will be the percentage of patients with improvement in alkaline phosphatase to less than 1.5 times normal over one year and the percentage of patients with a reduction in their Mayo Risk Score over one year.
    Time Frame
    1 year
    Secondary Outcome Measure Information:
    Title
    Effects of UDCA & budesonide on serum levels of alk phos, AST, total bilirubin, albumin, and prothrombin time, Mayo risk score and toxicity and tolerability of the budesonide/UDCA regimen, including effects on bone density.
    Time Frame
    1 year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    21 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Chronic cholestatic liver disease for greater than 6 months with alkaline phosphatase levels greater than 2 times the upper limit of normal. Positive AMA titer 1:40 or AMA > 1.0 U. Liver histology in the past (available for review) with features consistent with or diagnostic of PBC Ultrasound, computed tomography (CT), or cholangiography of the biliary tree which excludes biliary obstruction. The diagnosis of AIH necessary for evaluation of PBC-AIH overlap syndrome will be based on the revised International Autoimmune Hepatitis Group (IAHG) Scoring System. Exclusion Criteria: Patients with other serious coexistent conditions such as pre-existing advanced malignancy or severe cardiopulmonary disease which would be expected to limit their expectancy to less than three years. Patients unable to provide informed consent. Treatment with methotrexate, corticosteroids, azathioprine, chlorambucil, cyclosporin, penicillamine, colchicine or chenodeoxycholic acid in the preceding three months. Anticipated need for transplantation in one year (Mayo survival model <80% one-year survival without transplant). Liver biopsy revealing stage IV disease. Evidence of portal hypertension such as esophageal varices, portal gastropathy, ascites or hepatic encephalopathy. Known history of portal vein thrombosis. Evidence of osteoporosis. Serum bilirubin >4 mg/dl. Age less than 21 years of age or greater than 75 years of age. Pregnancy. Breast-feeding. Active drug or alcohol use. Findings highly suggestive of liver disease of other etiology such as chronic alcoholic liver disease, chronic hepatitis B or C infection, hemochromatosis, Wilson's disease, 1-antitrypsin deficiency, non-alcoholic steatohepatitis or sclerosing cholangitis. Serum creatinine over 2.0 mg/dl. History of documented active peptic ulcer disease in preceding year.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Keith D Lindor, MD
    Organizational Affiliation
    Mayo Clinic
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Links:
    URL
    http://clinicaltrials.mayo.edu
    Description
    Mayo Clinic Clinical Trials

    Learn more about this trial

    Oral Budesonide in the Treatment of Patients With Primary Biliary Cirrhosis and Overlap Features of Autoimmune Hepatitis

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